The efficacy of 5-HT3 receptor antagonists for the prevention of postoperative nausea and vomiting after craniotomy: a meta-analysis

The purpose of this meta-analysis was to assess the efficacy of prophylactic administration of 5-HT3 receptor antagonists for postoperative nausea and vomiting in neurosurgical patients at 24 and 48+ hours. After a systematic search, 7 published randomized placebo controlled trials involving 448 craniotomy patients (222 treatment, 226 control) were included in the meta-analysis. Study drugs included ondansetron, granisetron, and tropisetron. The cumulative incidence of emesis was significantly reduced in the treatment group at 24 hours [relative risk (RR)=0.50, 95% confidence interval (CI): 0.38-0.66] and 48+ hours (RR=0.52, 95% CI: 0.36-0.75). There were no differences between the treatment and control groups in the cumulative incidence of nausea at 24 hours (RR=0.76, 95% CI: 0.54-1.06) and 48+ hours (RR=0.81, 95% CI: 0.62-1.06). The cumulative incidence of both nausea and vomiting continued to increase after 24 hours in both groups. Despite the ability of 5-HT3 receptor antagonists to reduce emetic episodes, future investigations should seek to address the control of postoperative nausea and to reduce further postoperative emesis in this population.     

5-HT3 receptor antagonistsvs traditional agents for the prophylaxis of postoperative nausea and vomiting

PURPOSE: Numerous antiemetics have been studied for the prevention of postoperative nausea and vomiting (PONV) including traditional agents (metoclopramide, perphenazine, prochlorperazine, cyclizine and droperidol) and the 5-HT3 receptor antagonists (ondansetron, dolasetron, granisetron and tropisetron). The results have been divergent and inconsistent. The purpose of this quantitative systematic review was to evaluate the effectiveness of 5HT3 receptor antagonists compared to traditional antiemetics for the prevention of PONV METHODS: A systematic search of the English language literature using computerized MEDLINE, EMBASE, and Pre-MEDLINE databases from 1966 to October 1999 and a manual search of references from retrieved articles were performed. Individual efficacy and adverse effect data was extracted from each of the studies according to a predefined protocol. The summary odds ratios were calculated using the Dersimonian and Laird method under a random effects model. RESULTS: A total of 41 trials met our pre-defined inclusion criteria and were included in our analysis. Results in the 32 studies examining PONV indicated a 46% reduction in the odds of PONV in the 5-HT3-treated group (0.54 [95% CI 0.42-0.71], P < 0.001). Evaluation of PONV by traditional antiemetic agent demonstrated a 39% reduction compared with droperidol (0.61 [95% CI 0.42-0.89], P < 0.001) and a 56% reduction compared with metoclopramide (0.44 [95% CI 0.31-0.62], P < 0.001). Results in the 34 studies examining vomiting indicated a 38% reduction in the odds of vomiting in the 5-HT3-treated group (0.62 [95% CI 0.48-0.81], P < 0.001). CONCLUSIONS: The 5-HT3 receptor antagonists are superior to traditional antiemetic agents for the prevention of PONV and vomiting. The reduction in the odds of PONV and vomiting is significant in the overall analysis and the subgroup analyses comparing 5-HT3 receptor antagonists with droperidol and metoclopramide.     

Prophylaxis of postoperative nausea and vomiting: controversies in the use of serotonin 5-hydroxytryptamine subtype 3 receptor antagonists

Postoperative nausea and vomiting (PONV) continues to be a "big little problem" despite recent advances in anesthesia. Because of an increased interest in, and the abundant publications on this topic, guidelines for the management of PONV were published in 2003. Several key but controversial issues regarding PONV prophylaxis were left unaddressed, however. These included whether clinical differences exist between the 5-hydroxytryptamine subtype 3 (5-HT3) receptor antagonists, concern over optimal dosage and timing of administration, optimal 5-HT3 receptor antagonist combination therapy, and whether rescue therapy is effective after prior administration of the same or a different 5-HT3 receptor antagonist. The application of these antiemetics in clinical practice has raised questions regarding the role of the 5-HT3 receptor antagonists in the treatment of postdischarge nausea and vomiting and opioid-induced nausea and vomiting. A brief overview of the incidence, risk factors and current management recommendations for PONV and current controversies with special emphasis on the 5-HT3 receptor antagonists, is discussed.     

Prevention of postoperative nausea and vomiting using ondansetron, a new, selective, 5-HT3 receptor antagonist.

The effect of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting was investigated in a randomized, double-blind, placebo-controlled study of 84 patients undergoing gynecologic operation and receiving the same general anesthetic. The patients received premedication with either 16 mg oral ondansetron, or a matching placebo. The same medication was given postoperatively 8 h after the first dose. During the first hour after recovery from anesthesia, the frequencies of nausea and vomiting were 52% and 40%, respectively, in patients given placebos. In the ondansetron group nausea and vomiting developed in 17% and 12%, respectively, values significantly different from those with placebos (P less than 0.005). Similar differences were observed throughout the entire 24-h period after recovery, the incidence of nausea and vomiting being 67% and 60%, respectively, in the placebo group and 29% and 26% in the ondansetron treatment group. Ondansetron appears to be a promising antiemetic for the prevention of postoperative nausea and vomiting.     

Evidence-based management of postoperative nausea and vomiting

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Droperidol and 5-HT3-receptor antagonists, alone or in combination, for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomised controlled trials

BACKGROUND: Droperidol and 5-HT3-receptor antagonists are among the most potent antiemetics to prevent postoperative nausea and vomiting (PONV). Combinations of these drugs have been used to increase the efficacy of antiemetic treatment. However, so far the quantitative effect of this combination has not been evaluated systematically. METHODS: Results from randomised controlled trials investigating the efficacy of 5-HT3-receptor antagonists or droperidol alone versus the combination of both drugs to prevent PONV were included in a meta-analysis. Studies were systematically searched using Medline, EMBASE, the Cochrane-Library, and by manually screening the reference lists of matching review articles and current issues of locally available peer-reviewed anaesthesia journals. Seven papers with data on granisetron published by Fujii and co-workers were not considered. The main end point in each study was defined as occurrence of nausea, retching, or vomiting within 6 h ("early PONV") and within 48 h ("late PONV") after surgery. The relative risks (RR) and the numbers needed to treat (NNT) of the pooled data with their corresponding 95% confidence intervals (given in parentheses) were calculated using a random effects model. RESULTS: Eight studies with 881 patients (adults: n=801; children (mean age: 8 yr): n=80) were included in the analysis. Droperidol was applied to 340 patients, 5-HT3-receptor antagonists to 198, and 343 were treated with a combination of both drugs. Seven out of these eight studies reported increased antiemetic efficacy of the combination group compared with the single drugs (droperidol and 5-HT3-receptor antagonists respectively). However, in none of the trials did this difference reach statistical significance. When a meta-analytic analysis based on these results was performed the combination of droperidol with a 5-HT3-receptor antagonist was not associated with a significantly increased antiemetic efficacy. In 12 to 13 patients a 5-HT3-receptor antagonist has to be added to droperidol prophylaxis to prevent one additional patient from PONV who would have had suffered from PONV when treated with droperidol alone (RR "early PONV": 1.52 (0.95-2.44); RR "late PONV": 1.24 (0.89-1.74)). Similar results were obtained when the antiemetic effect of adding droperidol to a prophylaxis with 5-HT3-receptor antagonists was analysed. In this case 10 to 12 patients have to be treated with the 5-HT3-droperidol combination instead of with a 5-HT3-receptor antagonist alone to prevent one additional patient from PONV (RR "early PONV": 1.55 (0.68-3.52); RR "late PONV": 1.29 (0.77-2.17)). There were no reports of an increased incidence of adverse effects. CONCLUSION: The data on the combination of droperidol with 5-HT3-receptor antagonists suggest that there is a trend towards increased efficacy of the combination therapy compared to the single drugs. However, so far there are insufficient data to recommend this combination treatment for prophylaxis.     

Evidence-based management of postoperative nausea and vomiting: a review

PURPOSE: To provide evidence-based guidelines for the prophylaxis and treatment of postoperative nausea and vomiting (PONV). SOURCE: Literature from randomized controlled trials, systematic reviews, logistic regression analyses and expert opinion in the management of PONV. Principal findings: The etiology of PONV is multifactorial. Patient, anesthesia, and surgery related risk factors have been identified. Universal PONV prophylaxis is not cost-effective. Identification of patients at high-risk of PONV allows targeting prophylaxis to those who will benefit most from it. No prophylaxis is needed for patients at low risk for PONV. For patients at moderate risk for PONV, prophylaxis using a single antiemetic or a combination of two agents should be considered. Double and triple antiemetic combinations should be considered for patients at high risk for PONV. Furthermore, a multimodal approach should be adopted incorporating steps to keep the baseline risk of PONV low. The optimum cost-effective approach to the management of PONV will differ between an ambulatory centre and an inpatient hospital setting. For the treatment of established PONV in patients who failed prophylaxis, patients should not receive a repeat dose of the prophylactic antiemetic. Rather, a drug acting at a different receptor should be used. Beyond six hours after surgery, patients can be treated with any of the agents used for prophylaxis, except dexamethasone and transdermal scopolamine. CONCLUSION: PONV are common after anesthesia and surgery. We provided evidence-based guidelines for the management of this problem based on the available literature.     

Strategies for postoperative nausea and vomiting

Significant improvement towards a better control of postoperative nausea and vomiting have been achieved in recent years. Today, we understand better who is likely to vomit or to be nauseous after surgery. Significant amounts of the huge literature on anti-emetic interventions have been systematically reviewed, critically appraised and quantitatively synthesized. Thus, we know what anti-emetic interventions work, and how well they work, and we know their adverse effect profile. We also know which interventions have no worthwhile efficacy. A rational approach to postoperative nausea and vomiting includes three steps: identification of patients at risk, keeping the baseline risk low, and prophylactic administration of anti-emetics in those patients who are most likely to need them. For patients who are identified as high-risk patients, all measurements should be simultaneously initiated (multimodal anti-emesis).     

Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting

The present guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in postoperative nausea and vomiting (PONV) under the auspices of The Society of Ambulatory Anesthesia. The panel critically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. In brief, these guidelines identify risk factors for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic monotherapy and combination therapy regimens for PONV prophylaxis; recommend approaches for treatment of PONV when it occurs; and provide an algorithm for the management of individuals at increased risk for PONV.     

Controlling postoperative nausea and vomiting

Postoperative nausea and vomiting (PNV) in the ambulatory surgical unit is a continuing and vexing problem. Delayed discharges and patient discomfort have major impact in an outpatient setting. An understanding of the causes and aetiologies of PNV including anaesthetic, surgical and patient factors is critically important in the management of these patients. Therapy begins with a good history, identification of patients at risk, and the use of appropriate anaesthetic technique and agents, as well as prophylactic treatment. Aggressive postoperative treatment is also a necessity and good communication between the staff, and the patient and their family, is essential. Postoperative nausea and vomiting can be controlled in the outpatient setting, leading to better patient outcome and satisfaction, as well as a smoother and more efficiently functioning ambulatory unit.     

Risk factors for postoperative nausea and vomiting

Knowledge of postoperative nausea and vomiting (PONV) risk factors allows anesthesiologists to optimize the use of prophylactic regimens. Modern PONV risk research began in the 1990s with publication of studies using logistic regression analysis to simultaneously identify multiple independent PONV predictors and publication of meta-analyses and systematic reviews. This literature shows that female gender post-puberty, nonsmoking status, history of PONV or motion sickness, childhood after infancy and younger adulthood, increasing duration of surgery, and use of volatile anesthetics, nitrous oxide, large-dose neostigmine, or intraoperative or postoperative opioids are well established PONV risk factors. Possible risk factors include history of migraine, history of PONV or motion sickness in a child's parent or sibling, better ASA physical status, intense preoperative anxiety, certain ethnicities or surgery types, decreased perioperative fluids, crystalloid versus colloid administration, increasing duration of anesthesia, general versus regional anesthesia or sedation, balanced versus total IV anesthesia, and use of longer-acting versus shorter-acting opioids. Early-phase menstruation, obesity and lack of supplemental oxygen are disproved risk factors. Current risk scoring systems have approximately 55%-80% accuracy in predicting which patient groups will suffer PONV. Further research examining genetic and under-investigated clinical patient characteristics as potential risk factors, and involving outpatients and children, should improve predictive systems.